Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations

Ligase IV (LIG4) syndrome is a rare disorder of DNA damage repair caused by biallelic, pathogenic variants in LIG4. This is a phenotypically heterogeneous condition with clinical presentation varying from lymphoreticular malignancies in developmentally normal individuals to significant microcephaly, primordial dwarfism, radiation hypersensitivity, severe combined immunodeficiency and early mortality. Renal defects have only rarely been described as part of the ligase IV disease spectrum.We identified a consanguineous family where three siblings presenting with antenatal growth retardation, microcephaly, severe renal anomalies and skeletal abnormalities, including radial ray defects. Autozygosity mapping and exome sequencing identified a novel homozygous frameshift variant in LIG4, c.597_600delTCAG, p.(Gln200LysfsTer33), which segregated in the family. LIG4 is encoded by a single exon and so this frameshift variant is predicted to result in a protein truncated by 678 amino acids. This is the shortest predicted LIG4 protein product reported and correlates with the most severe clinical phenotype described to date. We note the clinical overlap with Fanconi anemia and suggest that LIG4 syndrome is considered in the differential diagnosis of this severe developmental disorder.     

基于半导体变温技术的离体肾脏保存箱温度控制系统的研制

肾移植是治疗终末期肾病综合症的主要方法之一,供体肾脏离体后的低温保存是影响手术成功的重要因素。本文阐述了一种简便、精度高、控制速度快的离体肾脏保存箱的温度控制系统的研制过程。该系统采用半导体变温技术来控制离体肾脏保存箱的温度,其测温传感器采用稳定性好、示值复现性高的铂电阻（Pt100）,温度控制策略采用PID控制。测试结果表明,系统在工作环境（23℃±2℃）条件下的温度过冲＜0.3℃,温度控制精度为±0.2℃,符合离体肾脏保存对温度的要求。     

Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C

Bryan CF, Luger AM, Smith JL, Warady BA, Wakefield M, Schadde E, Murillo D, Nelson PW. Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C.
Clin Transplant 2010: 24: 56–61. © 2009 John Wiley & Sons A/S.
Abstract:  The United Network for Organ Sharing (UNOS) implemented the virtual crossmatch system in UNet as a way to improve the likelihood of a negative crossmatch when kidneys are shared with HLA-sensitized candidates across donor service area (DSA) boundaries. The role of HLA C in that process is not universally appreciated. We recently experienced an unexpected positive flow T and B cell crossmatch for an imported, HLA zero-mismatched kidney because of donor-specific HLA C antibodies and transplanted it into the backup candidate. HLA C locus antigens were not typed by the OPO's laboratory that sent the kidney so the UNet virtual crossmatch could not "strike" our candidate from the UNOS match run. HLA C locus typing data of donors for kidneys our DSA imported from other DSAs revealed that C typing was not performed in 23% (14/60) and was discrepant with our molecular type for 10% (6/60) and was concordant in 67% (40/60) of cases. The rate of positive donor-specific crossmatches was higher (83%) for HLA C discrepantly typed donors than for concordantly typed donors (44%). Sensitization for HLA C (42%) is less frequent than for A (80%) or B (83%) locus antigens but the immunogenicity of C locus antigens in patients who make C locus antibodies is equivalent in black and white patients. Finally, the transplant rate of imported kidneys into class I-sensitized candidates was 24%, and C locus-sensitized candidates comprised 55% of those transplanted.     

Effect of procurement-related organ lesions on renal transplant outcome

Abstract: Background:  The purpose of our study was to examine the nature and incidence of renal injuries during organ procurement, to identify risk factors and to analyse the effects of organ lesions on the following transplantation.
Methods:  All cadaveric kidney transplantations performed at our centre from 1996 to 2006 with an organ donated within the Eurotransplant (ET) region were retrospectively analysed.
Results:  Five hundred and sixty-three renal grafts procured in 62 centres throughout the ET region were transplanted in the analysed period. One hundred and twenty (21.3%) kidneys were inadequately procured with 143 errors in total. The frequency of procurement errors did not differ significantly between kidneys procured by urologists and general surgeons (19.2% vs. 24.6%) nor when kidneys were procured alone or together with pancreas and/or liver (19.3% vs. 22.0%). Inadequate procurement lead to a discard rate of 0.2% and ultimately resulted in a surgical complication rate of 3.4%. Primary graft function (75.8% vs. 78.6%), three-yr graft survival (76.6% vs. 82.4%) and cumulated long-term graft survival were not significantly influenced by procurement errors.
Conclusion:  Additional measures to improve procurement quality are necessary. Nevertheless, adequate repair of organ lesions is possible and most organs can be successfully transplanted with very good short- and long-term results.     

Ultrashort intracorporeally maneuverable cryoprobes for laparoscopic renal cryoablation in the porcine model

AIM: To determine the feasibility and efficacy of laparoscopic renal cryosurgery using a novel ultrathin ultrashort intracorporeal cryoprobe in a porcine model. MATERIAL AND METHODS: Novel cryoprobes 4 cm in length and 1.5 mm in diameter were manipulated intracorporeally after insertion via a designated 15 mm laparoscopic port. Renal cryoablative lesions were induced laparoscopically in four 40 kg female piglets. We correlated between intraoperative temperature, ice ball geometry, intraoperative ultrasonographic properties, and histology. RESULTS: Laparoscopic manipulation of the cryoprobes was straightforward. No port site bleeding occurred during insertion, freezing, thawing or upon removal of the probes. The 0 degrees C, -20 degrees C, and -40 degrees C isotherms were measured at 6, 8, and 12 mm from the probe circumferentially. Ice-ball volume stabilization as determined by ultrasound occurred after 10 min of activation. Lower temperatures were reached after 10 min of probe activation as compared with 5 min (ice ball diameter 30 mm, DeltaT = 13-21 degrees C). Using a second 10-min-long freeze cycle resulted in a 14-22 degrees C lower temperature within the ice ball compared to a single cycle. Full coagulative necrosis was noted in the areas between the inserted probes with an additional 1-2 mm circumferential rim of severe tubular damage and apoptosis. CONCLUSIONS: Our novel cryoprobe can be used effectively and conveniently in laparoscopic renal cryosurgery. Considering the size of the cryogenic lesion, using a cluster of probes may be advisable.     

Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague-Dawley rats

Chromium is a widespread industrial compound. The soluble hexavalent chromium Cr (VI) is an environmental contaminant widely recognized as carcinogen, mutagen, and teratogen toward humans and animals. The fate of chromium in the environment is dependent on its oxidation state. The reduction of Cr (VI) to Cr (III) results in the formation of reactive intermediates leading to oxidative tissue damage and cellular injury. In the present investigation, Potassium dichromate was given intraperitoneally to Sprague-Dawley rats for 5 days with the doses of 2.5, 5.0, 7.5, and 10 mg/kg body weight per day. Oxidative stress including the level of reactive oxygen species (ROS), the extent of lipid peroxidation and the activity of antioxidant enzymes in both liver and kidney was determined. DNA damage in peripheral blood lymphocytes was determined by single-cell gel electrophoresis (comet assay). The results indicated that administration of Cr (VI) had caused a significant increase of ROS level in both liver and kidney after 5 days of exposure, accompanied with a dose-dependent increase in superoxide dismutase and catalase activities. The malondialdehyde content in liver and kidney was elevated as compared with the control animals. Dose- and time-dependent effects were observed on DNA damage after 24, 48, 72, and 96 h posttreatment. The results obtained from the present study showed that Cr (VI) could induce dose- and time-dependent effects on DNA damage, both liver and kidney show defense against chromium-induced oxidative stress by enhancing their antioxidant enzyme activity. However, liver was found to exhibit more antioxidant defense than the kidney.     

Polycystic kidney and hepatic disease with mental retardation and hand anomalies in three siblings

A family with three children affected with congenital polycystic kidneys, hepatic fibrosis, mental retardation, minor anomalies of the hands, and dysmorphic facial features is reported. All children progressed to chronic renal failure. Linkage to the locus for autosomal recessive polycystic kidney disease was excluded by haplotype analysis. The family is endogamic, and the affected siblings are of both sexes, which is in agreement with an autosomal recessive determination of this syndrome. A similar syndrome was reported in 1990 by Labrune et al. [J Pediatr Gastroenterol Nutr (1990) 10:540–543]. Our report provides further evidence for the etiological heterogeneity of polycystic kidney with hepatic fibrosis. The syndrome reported here should be considered in the differential diagnosis of the early manifestation of polycystic kidneys. Mental retardation and hand anomalies are the hallmarks for the differential diagnosis of this syndrome.     

A case of de novo glomerulonephritis with electron-dense deposits following renal transplantation

Abstract:  We present here a case of de novo glomerulonephritis (GN) two yr after kidney transplantation. The patient was a 13-yr-old girl who had renal insufficiency because of bilateral hypoplastic kidneys. She received a renal allograft from her father at the age of 11 yr. Immunosuppressive treatment was started with tacrolimus, mizoribine (MZB), basiliximab, and methylprednisolone (mPSL). There were no findings of GN at the one-h biopsy (first biopsy). Two yr after transplantation, she showed proteinuria, hematuria and increased serum creatinine level with no apparent trigger. The biopsy specimen (fourth) showed mesangial proliferative GN with electron-dense deposits in a variety of regions and borderline changes indicating acute rejection. She was treated with mPSL pulse therapy, deoxyspergualin, replacement of MZB with mycophenolate mofetil, an increase of the mPSL dose, and candesartan. Her serum creatinine and urinary protein excretion levels improved after the treatment. One month later, she developed deterioration in her renal function again. Renal biopsy findings (fifth) were almost the same as the lesions observed in the fourth allograft biopsy. After she recovered from these episodes, she appeared to improve in clinical findings of GN. Protocol biopsies at three yr and five months after transplantation (sixth) showed no evidence of acute rejection, but we still observed the features of de novo GN. We could not resolve the underlying causes by reference to the clinical history and serological findings. We speculate that some kind of immunological reactions might be associated with the pathophysiology.     

Solving the Organ Shortage Crisis: The 7th Annual American Society of Transplant Surgeons' State-of-the-Art Winter Symposium

The 2007 American Society of Transplant Surgeons' (ASTS) State-of-the-Art Winter Symposium entitled, 'Solving the Organ Shortage Crisis' explored ways to increase the supply of donor organs to meet the challenge of increasing waiting lists and deaths while awaiting transplantation. While the increasing use of organs previously considered marginal, such as those from expanded criteria donors (ECD) or donors after cardiac death (DCD) has increased the number of transplants from deceased donors, these transplants are often associated with inferior outcomes and higher costs. The need remains for innovative ways to increase both deceased and living donor transplants. In addition to increasing ECD and DCD utilization, increasing use of deceased donors with certain types of infections such as Hepatitis B and C, and increasing use of living donor liver, lung and intestinal transplants may also augment the organ supply. The extent by which donors may be offered incentives for donation, and the practical, ethical and legal implications of compensating organ donors were also debated. The expanded use of nonstandard organs raises potential ethical considerations about appropriate recipient selection, informed consent and concerns that the current regulatory environment discourages and penalizes these efforts.     

Short rib-polydactyly (SRP) syndromes,types Majewski and Saldino-Noonan

Four examples of short rib-polydactyly syndromes are described. Case 1 represents the Majewski type, and the other three are examples of the Saldino-Noonan type. Both conditions are true multiple congenital anomaly syndromes and neonatally lethal forms of dwarfism with a narrow thorax, polydactyly and associated visceral malformations. They are probably caused by the homozygous state of different autosomal recessive genes. They must be differentiated from similar conditions such as chondroectodermal dysplasia, asphyxiating thoracic dysplasia, the Meckel syndrome and the trisomy 13 syndrome.The short rib-polydactyly syndrome type Majewski is characterized by thoracic dystrophy, pre- and postaxial polydactyly, mesomelic brachymelia and cleft lip and/or palate. Skull, vertebral column and pelvis are not markedly affected. Associated features include polycystic kidneys, hypolastic epiglottis and lungs, and various malformations of the cardiovascular system, genitalia and the central nervous system.The short rib-polydactyly syndrome type Saldino-Noonan is characterized by thoracic dystrophy, postaxial polydactyly, severely shortened, flipper-like extremities and a striking metaphyseal dysplasia of the tubular bones. The ossification of the calvaria, vertebral column, pelvis and short bones of the hands and feet is defective. Associated features occurring in varying frequency include polycystic kidneys, transposition of the great vessels and atretic lesions of the gastrointestinal and genitourinary systems.

---

Zusammenfassung Es wird über 4 Fälle mit Thoraxdysplasie-Polydaktylie-Syndromen berichtet. Fall 1 wird dem Majewski-Typ, die Fälle 2–4 werden dem Saldino-Noonan-Typ dieser Syndrome zugeordnet. Es handelt sich um letale Zwerg-wuchsformen mit eigenartigen Mißbildungsmustern. Sie sind wahrscheinlich durch Homozygotie autosomal recessiver Gene bedingt. Differentialdiagnostisch sind sie in erster Linie von der chondroektodermalen Dysplasie (Ellis-van Creveld-Syndrom), der asphyxierenden Thoraxdysplasie, dem Meckel-Syndrom und der Trisomie 13 abzugrenzen.Der Majewski-Typ der Thoraxdysplasie-Polydaktylie-Syndrome ist charakterisiert durch kurze Rippen, prä- und postaxiale Polydaktylie, eine mesomele Brachymelie und Spaltbildungen im Lippen-Kiefer-Gaumen-Bereich. Weitere Merkmale sind Nierencysten, eine Hypoplasie von Epiglottis und Lungen, verschiedene Fehlbildungen von Herz, großen Gefäßen, Zentralnervensystem und Genitalien.Der Saldino-Noonan-Typ der Thoraxdysplasie-Polydaktylie-Syndrome ist gekennzeichnet durch kurze Rippen, postaxiale Polydaktylie, eine schwere Verkürzung der Gliedmaßen und eine ausgeprägte metaphysäre Dysplasie der Röhrenknochen. Es bestehen erhebliche Ossifikationsstörungen der kurzen Röhrenknochen, leichtere der Schädelkalotte und Wirbelkörper. Das Becken ähnelt dem bei der chondroektodermalen Dysplasie und der asphyxierenden Thoraxdysplasie. Begleitfehlbildungen sind Nierencysten, Transposition der großen Gefäße und Atresien im Bereich des Gastrointestinal- und Urogenitaltrakts.